Clear-cell carcinoma of the ovary (CCCO) is a distinct entity of epithelial ovarian cancer in terms of clinical, histopathological, or genetic features. The incidence of CCCO is different by ethnicity but the reason is not clear yet. Overall prognosis of CCCO is good because most CCCO is found in stage I. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. The same is true for recurrent disease. Therefore, genetic analysis of CCCO is important to find the right target(s) and better therapeutic approaches. Because of its rarity, international collaboration is necessary to conduct randomized clinical trials for CCCO.

Background Endometrial mesonephric-like adenocarcinomas exhibit classical histologic features of mesonephric carcinoma; however, it remains unclear whether these tumors represent mesonephric (Wolffian) carcinoma or endometrioid (Müllerian) carcinomas that closely mimic mesonephric carcinoma. Case presentation A 32-year-old Japanese primigravida presented with atypical vaginal bleeding. An endometrial biopsy suggested low-grade endometrioid carcinoma, and she was administered medroxyprogesterone acetate. Her tumor recurred 6 years later, and she underwent hysterectomy, salpingo-oophorectomy, and omentectomy, at which point she was diagnosed with mesonephric-like adenocarcinoma of the uterine endometrium. Retrospective pathological review of the initial biopsy confirmed coexisting low-grade endometrioid carcinoma and mesonephric-like adenocarcinoma of the uterine endometrium. On immunohistochemistry, the endometrioid carcinoma component was diffuse positive for estrogen and progesterone receptors but negative for thyroid transcription factor 1. However, the mesonephric-like adenocarcinoma component exhibited a mixture of estrogen receptor- and thyroid transcription factor 1-positive cells within the same glands. Conclusions We encountered a patient with coexisting endometrial mesonephric-like adenocarcinoma and low-grade endometrioid carcinoma, which was treated using medroxyprogesterone acetate therapy, resulting in recurrence of mesonephric-like adenocarcinoma alone. These clinicopathological findings support the prevailing notions that mesonephric-like adenocarcinoma is a Müllerian adenocarcinoma exhibiting mesonephric differentiation.

Low-grade and early-stage endometrial cancer usually has a favorable prognosis, whereas recurrent or metastatic disease is often difficult to cure. Thus, the molecular mechanisms underlying advanced pathophysiology remain to be elucidated. From the perspective of the origin of advanced endometrial cancer, the characterization of cancer stem-like cells (CSCs) will be the first step toward the development of clinical management. We established long-term culturable patient-derived cancer cells (PDCs) from patient endometrial tumors by spheroid cell culture, which is favorable for the enrichment of CSCs. PDC-derived xenograft tumors were generated in immunodeficient NOD/Shi-scid, IL-2RγKO Jic mice. Morphologically, PDCs derived from three distinct patient samples and their xenograft tumors recapitulated the corresponding original patient tumors. Of note, CSC-related genes including ALDH1A1 were upregulated in all of these PDCs, and the therapeutic potentiality of aldehyde dehydrogenase inhibitors was demonstrated. In addition, these PDCs and their patient-derived xenograft (PDX) models exhibited distinct characteristics on the basis of their hormone responsiveness and metastatic features. Interestingly, genes associated with inflammation and tumor immunity were upregulated by 17β-estradiol in PDC lines with high estrogen receptor expression and were also overexpressed in secondary PDCs obtained from metastatic tumor models. These results suggest that PDC and PDX models from endometrial cancer specimens would be useful to elucidate CSC traits and to develop alternative diagnostic and therapeutic options for advanced disease.

From a series of cancer patients, we report a patient diagnosed with TD without the typical clinical symptoms of WE at the preoperative psychiatric examination.ResultA 43-year-old woman with ovarian cancer was referred by her oncologist to the psycho-oncology outpatient clinic for preoperative psychiatric evaluation. Her tumor had been growing rapidly before the referral. Although she did not develop delirium, cerebellar signs, or eye symptoms, we suspected she might have developed TD because of her 2-month loss of appetite as the storage capacity of thiamine in the body is approximately 18 days. The diagnosis of TD was supported by abnormally low serum thiamine levels.Significance of resultsCancer therapists need to be aware that thiamine deficiency may occur even before the start of cancer treatment. In cases with a loss of appetite of more than 2 weeks' duration, in particular, thiamine deficiency should be considered if the tumor is rapidly increasing, regardless of the presence or absence of delirium.

Purpose Circulating tumor DNA (ctDNA) is an attractive source for liquid biopsy to understand molecular phenotypes of a tumor non-invasively, which is also expected to be both a diagnostic and prognostic marker. PIK3CA and KRAS are among the most frequently mutated genes in epithelial ovarian cancer (EOC). In addition, their hotspot mutations have already been identified and are ready for a highly sensitive analysis. Our aim is to clarify the significance of PIK3CA and KRAS mutations in the plasma of EOC patients as tumor-informed ctDNA. Methods We screened 306 patients with ovarian tumors for somatic PIK3CA or KRAS mutations. A total of 85 EOC patients had somatic PIK3CA and/or KRAS mutations, and the corresponding mutations were subsequently analyzed using a droplet digital polymerase chain reaction in their plasma. Results The detection rates for ctDNA were 27% in EOC patients. Advanced stage and positive peritoneal cytology were associated with higher frequency of ctDNA detection. Preoperative ctDNA detection was found to be an indicator of outcomes, and multivariate analysis revealed that ctDNA remained an independent risk factor for recurrence (p=0.010). Moreover, we assessed the mutation frequency in matched plasma before surgery and at recurrence from 17 patients, and found six patients had higher mutation rates in cell-free DNA at recurrence compared to that at primary diagnosis. Conclusion The presence of ctDNA at diagnosis was an indicator for recurrence, which suggests potential tumor spread even when tumors were localized at the time of diagnosis.